T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity

Meningeal ectopic lymphoid follicle (eLF)–like structures have been described in multiple sclerosis, but their role in central nervous system (CNS) autoimmunity is unclear. Here, we used a T helper 17 (T_H17) adoptive transfer experimental autoimmune encephalomyelitis model featuring formation of eLFs. Single-cell RNA sequencing revealed that clusters of activated B cells and B1/marginal zone–like B cells were overrepresented in the CNS and identified B cells poised for undergoing germinal center reactions and clonal expansion in the CNS. Using intravital imaging to directly visualize T_H17–B cell interactions, we demonstrated that T and B cells form long-lasting antigen-specific contacts in meningeal eLFs that result in reactivation of autoreactive T cells. CNS T cells depended on CNS B cells to maintain a proinflammatory cytokine profile. Our study reveals that extensive T–B cell cooperation occurs in meningeal eLFs, promoting both B cell differentiation and T cell reactivation, and may thereby propagate smoldering inflammation in the CNS.